Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/128313
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dc.contributor.authorMontgomery, M.K.-
dc.contributor.authorBayliss, J.-
dc.contributor.authorDevereux, C.-
dc.contributor.authorBezawork-Geleta, A.-
dc.contributor.authorRoberts, D.-
dc.contributor.authorHuang, C.-
dc.contributor.authorSchittenhelm, R.B.-
dc.contributor.authorRyan, A.-
dc.contributor.authorTownley, S.L.-
dc.contributor.authorSelth, L.A.-
dc.contributor.authorBiden, T.J.-
dc.contributor.authorSteinberg, G.R.-
dc.contributor.authorSamocha-Bonet, D.-
dc.contributor.authorMeex, R.C.R.-
dc.contributor.authorWatt, M.J.-
dc.date.issued2020-
dc.identifier.citationScience Translational Medicine, 2020; 12(559):1-13-
dc.identifier.issn1946-6234-
dc.identifier.issn1946-6242-
dc.identifier.urihttp://hdl.handle.net/2440/128313-
dc.description.abstractIntertissue communication is a fundamental feature of metabolic regulation, and the liver is central to this process. We have identified sparc-related modular calcium-binding protein 1 (SMOC1) as a glucose-responsive hepatokine and regulator of glucose homeostasis. Acute intraperitoneal administration of SMOC1 improved glycemic control and insulin sensitivity in mice without changes in insulin secretion. SMOC1 exerted its favorable glycemic effects by inhibiting adenosine 3',5'-cyclic monophosphate (cAMP)-cAMP-dependent protein kinase (PKA)-cAMP response element-binding protein (CREB) signaling in the liver, leading to decreased gluconeogenic gene expression and suppression of hepatic glucose output. Overexpression of SMOC1 in the liver or once-weekly intraperitoneal injections of a stabilized SMOC1-FC fusion protein induced durable improvements in glucose tolerance and insulin sensitivity in db/db mice, without adverse effects on adiposity, liver histopathology, or inflammation. Furthermore, circulating SMOC1 correlated with hepatic and systemic insulin sensitivity and was decreased in obese, insulin-resistant humans. Together, these findings identify SMOC1 as a potential pharmacological target for the management of glycemic control in type 2 diabetes.-
dc.description.statementofresponsibilityMagdalene K. Montgomery, Jacqueline Bayliss, Camille Devereux, Ayenachew Bezawork-Geleta ... Scott L. Townley, Luke A. Selth ... et al.-
dc.language.isoen-
dc.publisherAmerican Association for the Advancement of Science-
dc.rights© 2020, Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. https://www.sciencemag.org/about/science-licenses-journal-article-reuseThis is an article distributed under the terms of the Science Journals Default License.-
dc.source.urihttp://dx.doi.org/10.1126/scitranslmed.aaz8048-
dc.subjectLiver-
dc.subjectAnimals-
dc.subjectMice, Inbred C57BL-
dc.subjectMice-
dc.subjectDiabetes Mellitus, Type 2-
dc.subjectInsulin Resistance-
dc.subjectInsulin-
dc.subjectGlucose-
dc.subjectBlood Glucose-
dc.subjectGlycemic Control-
dc.titleSMOC1 is a glucose-responsive hepatokine and therapeutic target for glycemic control-
dc.typeJournal article-
dc.identifier.doi10.1126/scitranslmed.aaz8048-
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1156508-
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1098972-
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1077703-
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1143224-
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1077703-
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1143224-
pubs.publication-statusPublished-
dc.identifier.orcidSelth, L.A. [0000-0002-4686-1418]-
Appears in Collections:Aurora harvest 8
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